CN107530358A - Gel capsule containing sterol and solubilizer - Google Patents

Gel capsule containing sterol and solubilizer Download PDF

Info

Publication number
CN107530358A
CN107530358A CN201680022726.2A CN201680022726A CN107530358A CN 107530358 A CN107530358 A CN 107530358A CN 201680022726 A CN201680022726 A CN 201680022726A CN 107530358 A CN107530358 A CN 107530358A
Authority
CN
China
Prior art keywords
preparaton
ester
sterol
acid
gel capsule
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201680022726.2A
Other languages
Chinese (zh)
Other versions
CN107530358B (en
Inventor
J·吉尔克
M·韦德纳
M·黑尔
T·施梅勒
T·黑尔加松
H·伯恩
A·魏兰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of CN107530358A publication Critical patent/CN107530358A/en
Application granted granted Critical
Publication of CN107530358B publication Critical patent/CN107530358B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/20—Ingredients acting on or related to the structure
    • A23V2200/238—Solubility improving agent
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/18—Lipids
    • A23V2250/184—Emulsifier
    • A23V2250/1842—Lecithin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/18—Lipids
    • A23V2250/186—Fatty acids
    • A23V2250/1882—Polyunsaturated fatty acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A23V2250/2136—Phytosterols, phytostanols
    • A23V2250/21368—Phytosterols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Nutrition Science (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Medicinal Preparation (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • General Preparation And Processing Of Foods (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Jellies, Jams, And Syrups (AREA)

Abstract

The present invention relates to the gel capsule comprising sterol and solubilizer as food supplement or as medicine.

Description

Gel capsule containing sterol and solubilizer
The present invention relates to the gel capsule comprising sterol and solubilizer as food supplement or as medicine.
Gel capsule is known per se：So-called hard shell capsules and soft capsule be present.It produces, for the raw material used in this and Its production is well-known to those skilled in the art.
Gel capsule comprising sterol is also known as food supplement or as the purposes of medicine.
Because sterol is only slightly soluble in water very much, therefore oil generally is used as into solvent.
Sterol ester is preferably solvable, but is generally equally dissolved in oil or fatty material at present.
Because sterol and sterol ester are so used so that they are prepared in oil, the preparaton of notable ratio is Oil.However, therefore per dosage unit, i.e., the preparation dosage that such as gel capsule can be supplied is because the maximum of gel capsule can connect It is limited by size.If the only a part preparaton is used up by oil, the amount for the sterol that can be supplied or the amount of sterol ester are further It is limited.In order to which so that each adult 2-3g amount provides the free sterol of recommended daily, the direction of effort is to need daily There is provided it is minimum can energy gel capsule, and gel capsule also should be extraly as small as possible；This adds " biddability " first, I.e. patient is observed correct dose, and therefore entirety improves treatment effect.In addition, in the case of food supplement, use The effect that the degree of recognition at family improves and therefore final same improvement is intervened.
In order to improve the validity of sterol ester preparaton, sterol ester and other compositions necessarily be formed miniemulsion, specifically Under pH even in low shear rate and stomach.This is in the case of pharmaceutical formulation by self-emulsifying systems in pharmaceutical industries Realize.However, this is directed to use with larger numbers of diluent materials and emulsifying agent.Similarly, in the case of pharmaceutical formulation, prison Pipe have approved a large amount of emulsifying agents, and therefore adjust the preparaton to obtain self-emulsifying systems comparatively than the situation letter of food It is single.In addition, the pharmaceutical actives quality to be given of per unit dose is generally significantly lower than in food in such self-emulsifying systems The situation of material in field.
In the case where per unit dose gives sterol ester, the amount is per unit dose about 1-3g, and when the dosage will When being configured to capsule, treat that the preparaton total amount of dosing is therefore very big.In field of food, because compared with medicinal application The number of emulsifying agent and surfactant is greatly limited in terms of supervision angle and can use the performance width of emulsifying agent therefore also very Limited, it is a significantly larger challenge to obtain self-emulsifying systems with the emulsifying agent and surfactant of a small amount of food approved.Stomach In low pH pass through neutralize reduce anion surfactant activity.Therefore, the effective preparaton for currently lacking sterol ester exists Availability in capsule, (giving 1 or at most 2 capsule daily) this time or at most is administered twice, thus with sterol ester Form provide daily amount sterol.
Therefore, it is intended that the preparaton of sterol and sterol ester in gel capsule is improved to for a gel capsule Weight percent of the sterol in the preparaton is based on the maximized degree of free sterol.
Known sterol especially phytosterol, i.e., the sterol obtained by plant.
In principle, sterol ester is all esters be possible to carboxylic acid.It is however, generally only right in food and health field It is interested with the ester of aliphatic acid.
It is known how the sterol ester of production aliphatic acid；The most frequently used method is to be produced by esterification by sterol and aliphatic acid. By the reaction can needed for substantially any in a manner of control conversion and therefore also control the purity of sterol ester.Generally labour for At least 80% is converted into sterol ester；Up to basic 100% conversion ratio is known and technically feasible.Higher purity also may be used With by purifying such as crystallization, cold filter realization.Such all method are well-known.
It has been found that for gel capsule the basic preparaton comprising sterol ester and emulsifying agent (also referred to as solubilizer) with And there is the gel capsule for including the preparaton.
Thus, the toatl proportion for " substantially " referring to the preparaton is at least 61 weight %.
In the context of the present invention, " solubilizer " is usually directed to the material to be worked in a manner of emulsifying and/or stabilize simultaneously And also synonymously it is referred to as " emulsifying agent " or " surfactant " in the context of the present invention.
In principle any sterol ester from any sterol can be used as sterol ester.It is preferred that use the steroid from plant Alcohol (" phytosterol "), this is well-known to those skilled in the art.In the context of the present invention, unless otherwise bright Really explanation, term " sterol " and " phytosterol " also include its hydrogenated analogs, " stanols ".
Particularly preferably (non-then to hydrogenate) sterol.
Sterol and stanols, especially sterol, are preferably esterified with aliphatic acid.Any aliphatic acid can be used as fat in principle Acid.It is preferred that the aliphatic acid obtained by natural origin, especially from those of plant and marine source, or corresponds respectively to it , but synthetically produced aliphatic acid.Particularly preferred plant or the aliphatic acid of marine source.Aliphatic acid can be used as pure material or Used as the substance migration for mainly including one or more aliphatic acid, or as the mixture of many different aliphatic acid.
It is preferred that use the aliphatic acid with extra health benefits.Such has the aliphatic acid of extra health benefits especially single Unsaturated and polyunsaturated fatty acid such as omega-fatty acid, EPA and DHA；All these aliphatic acid, its production, obtain and purify It is well-known to those skilled in the art.
Sterol ester can also include free sterol, i.e. no esterification sterol in the context of the present invention.Sterol ester used is steroid The mixture of alcohol ester and free sterol, wherein sterol ester content are preferably at least 80mol%, and particularly preferably at least 90mol% is non- Often particularly preferably at least 95mol%, especially at least 98mol% (based on the sterol ratio in the ester) and the sterol ester contains Amount can be all values and at most 100% between these ranges.
Therefore, sterol is preferably comprised for the preparaton of the present invention of gel capsule and the gel capsule comprising the preparaton Ester, especially with preferred plant or single insatiable hunger of marine source and/or how unsaturated, the steroid of particularly preferred polyunsaturated fatty acid Alcohol ester, at least one solubilizer, it is preferably selected from polysorbate such as TWEEN-20,40,60 and 80, lecithin lipid and tristearin Acyl -2- sodium lactates, particularly preferably selected from polysorbate 80 (polyoxyethylene (20) dehydrating sorbitol monooleate, E433), Lecithin lipid and esterification degree are 100-140 stearoyl -2- sodium lactates, very particularly preferably polysorbate 80 and/or lecithin Lipid.Particularly preferably use at least two different emulsifying agents.
Lecithin lipid refer in the context of the present invention comprising it is a certain proportion of preferably by any natural plants or animal Lai The composition for the lecithin lipid that source obtains.Such source and lecithin lipid is obtained by it is to those skilled in the art It is well known that for example from egg, soybean, sunflower, rapeseed.Lecithin lipid is preferably to include in the context of the present invention The mixing of lecithin lipid fraction, lysolecithin class (such as hydrolyzed lecithin class, enzyme urge the lecithin lipid of processing) and/or phospholipid Thing, by all plants and/or animal origin, preferred plant source such as rapeseed, sunflower and/or soybean obtain, especially excellent for it Such mixture obtained by soybean is selected, very particularly preferably includes at least 40%, 45%, 50%, 55%, 60%, 65%, 70% or 75% or greater percentage of phosphatidyl choline and at least 3%, 4%, 5%, 6% or 7% phosphatidyl-ethanolamine are somebody's turn to do Class mixture-wherein total amount is always the commercially available prod of 100%-such as Lecico series, such as soybean lecithin class Lecico F 600, Lecico F 580, Lecico F300, Lecico F 200, Lecico F 100, Lecico P900, Lecico P 700, Lecico P 300, sunflower lecithin class Lecico SUN 400, Lecico SUN FM 580, rapeseed lecithin Class Lecico RAP 200, Lipoid and Phospholidon series commercially available prod, such as Lipoid P45, Lipoid P75, Lipoid P75-3, Lipoid P100, Lipoid H100, Lipoid R100, Lipoid P100-3, Lipoid S45, Lipoid S75, Phospholidon 80H, Phospholidon 90H, Phospholidon 90G, preferably each have Have at least 60%, 65%, 70% or 75%, 80%, 85%, 90%, 95% or greater percentage of phosphatidyl choline, especially such as Lipoid P75, Lipoid S75, Lipoid P75-3, Lipoid P100-3, Phospholidon 80H, Phospholidon 90H, Phospholidon 90G, very particularly preferably there is about 65-75%, especially about 70% ratio Phosphatidyl choline those.
In addition, the gel capsule for the preparaton of gel capsule and comprising the preparaton can also include water, alcohol or Its mixture.The preparaton that lecithin lipid is preferably comprised as stabilizer also includes water and/or alcohol, particularly preferably mainly or very Mainly include alcohol.Thus, refer to " very much mainly " that alcohol can additionally include the water of residual quantity.The residual quantity is in alcohol In ratio be preferably smaller than 5 weight %, less than 4 weight %, less than 3 weight %, less than 2 weight %, less than 1 weight % or even Less than 0.5 weight %.
In another embodiment, oil is included comprising preparaton of the lecithin lipid as solubilizer for gel capsule, Especially vegetable oil such as sunflower oil.However, oil mass preferably wants small compared with the amount of sterol ester and is only large enough to realize sterol ester With the uniform dissolution of lecithin lipid.
Other compositions are possible to preparaton of the present invention, but they reduce the sterol amount that can be prepared.Therefore, only preferred pair Those necessary additives for preparation, such as the stabilizer for sterol ester, such as antioxidant, and also sugar ester, such as The list of aliphatic acid and carbohydrate, single-, two- and three esters, preferably palmitic acid and sucrose the monoesters of preferably sucrose, stearic acid and sucrose The monoesters of ester and/or oleic acid and sucrose.Conventional and suitable antioxidant is many institute's weeks to those skilled in the art Know.Therefore, preferably comprised for the invention described above preparaton of gel capsule and the gel capsule comprising the preparaton few Antioxidant is measured, hindered phenolic antioxidants are preferably selected from, such as tert-butyl hydroxy toluene, butylhydroxy anisole, the tert-butyl group Hydroxyquinone；Tocopherols such as α-, β-, γ-and Delta-Tocopherol or the mixture for including in these tocopherols at least two；Comprising At least two α in these tocotrienolses-, β-, γ-and δ-tocotrienols mixture；Comprising above-mentioned substance and/ Or phenols diterpene such as carnosol, carnosic acid, Polyphenols such as Epigallo-catechin gallate (EGCG), tannic acid and/or different The natural extract of at least one of flavonoids；Especially tocopherols, ascorbic acid or arabo-ascorbic acid or its suitable derivative Ester of the thing such as with aliphatic acid, such as ascorbyl palmitate and aliphatic acid acid ascorbyl ester.It is preferred that tocopherols and aliphatic acid resist Bad hematic acid ester, especially tocopherols and ascorbyl palmitate.
Preparaton of the present invention includes the material of following amounts：
Sterol ester:
It is at least 60 weight %, 65 weight % or preferably at least 70 weight % based on whole preparaton, particularly preferably at least 75 weight %, very particularly preferably at least 80 weight %, such as particularly preferred at least 85 weight % or even at least 88 weight %, its Packing material as gel capsule, for example, 60,61,62,63,64,66,67,68,69,71,72,73,74,76,77,78, 79th, 81,82,83,84,86,87,89,90 weight %.
Solubilizer：
In the case of lecithin lipid and comprising lecithin lipid fraction and phospholipid：At least 1 weight %, preferably at least 1.1 weight %, at least particularly preferably 1.2 weight %, very particularly preferably at least 1.3 weight %, especially at least 1.4 weight % As lower limit and at most 20 weight %, preferably up to 15 weight %, particularly preferably particularly preferably at most 10 weight %, at most 5 weights Measure % and be used as the upper limit, in each case based on whole preparaton, its packing material as gel capsule, such as 1.5.1.6, 1.7th, 1.8,1.9,2.0,2.1,2.2,2.3,2.4,2.5,2.6,2.7,2.8,2.9,3.0,3.5,4.0,4.5,5.0 weight % And all therebetween values；
In the case of polysorbate such as polysorbate 80 and fatty acyl -2- lactates：It is based on whole preparaton At least 5, preferably at least 5.5, particularly preferably at least 6.0, very particularly preferably at least 6.5, especially at least 7.0 weight %, its Packing material as gel capsule, such as 5.1,5.2,5.3,5.4,5.6,5.7,5.8,5.9,6.1,6.2,6.3,6.4, 6.6th, 6.7,6.8,6.9,7.1,7.2,7.3,7.4,7.5,7.6,7.7,7.8,7.9,8.0,8.1,8.2,8.3,8.4,8.6, 8.7、8.8、8.9、9.0、9.1、9.2、9.3、9.4、9.5、9.6、9.7、9.8、9.9、10.0、10.1、10.2、10.3、10.4、 10.5、10.6、10.7、10.8、10.9、11.0、11.5、12.0、12.5、13.0、13.5、14.0、14.5、15.0、15.5、 16.0th, 16.5,17.0,17.5,18.0,18.5,19.0,19.5,20.0 weight % and all therebetween values.
Water：
Water can exist with 0-25 weight % amount.When using polysorbate as unique solubilizer, the water that uses Amount is 0-15 weight %, preferably 0-10 weight % based on whole preparaton, and it is used as the packing material of gel capsule, and also has All values between these end points.Thus, " a small amount of ", which refers to exist in the preparaton, is no more than 10%, does not preferably surpass Cross 5% water.
When using lecithin lipid and mixture comprising lecithin lipid fraction and phospholipid as unique solubilizer, make Water is 0-25 weight %, preferably 5-23 weight % based on whole preparaton, and particularly preferred 10-20 weight %, it is used as The packing material of gel capsule, and also have all values between these end points.Thus, " a small amount of " refers in the preparation Exist in agent and be no more than 20%, preferably more than 15% water.
Oil：
Oily or a variety of oil can be based on whole preparaton with 0-25 weight %, but preferably more than 20 weight %, especially excellent Choosing is no more than 15 weight %, very particularly preferably exists no more than 10 weight %, the particularly preferably amount no more than 5 weight %.It is " few Amount ", which refers to exist in the preparaton, is no more than 10%, preferably more than 5% oil.
In principle, suitable oil is all natural and synthesis source oil (i.e. triglycerides), but preferred natural origin Oil, especially plant or marine source oil, the unusual especially oil of plant origin, such as from sunflower, linseed, Asia The oil of fiber crops, Ji, almond, rapeseed, coconut, palm etc. or its mixture, as those skilled in the art are well-known Like that.It is preferred that using with low ratio saturated fatty acid and/or unsaturated at high proportion and especially polyunsaturated fatty acid Oil, because they bring extra healthy advantage when in use, and it is preferred that should be by saturated fatty acid and especially trans-fatty Acid avoids being technically possible and/or commercial degree tolerable (i.e. especially for cost).
It is therefore preferable that with low amounts it is trans-aliphatic acid, preferably smaller than 5,4,3,2 or even 1% or less trans-fatty Acid fatty acid mixt, and/or the saturated fatty acid amount preferably having be less than 7%, preferably smaller than 6,5,4,3 or even 2 or 1% saturated fatty acid, the gross mass in each case based on aliphatic acid in the mixture.
Particularly preferred preparaton does not include any oil.
As other compositions, preferably it is based on whole preparaton using ascorbyl palmitate and sugar ester, respective amount At most 20 weight %, preferably up to 15 weight %, particularly preferably at most 10 weight %, especially up to 5 weight %, it is used as solidifying The packing material of glue capsule.It is preferred that at least 1% is used in each case, such as 1.5,2,2.5,3,3.5,4 or 4.5 weights Measure %.
Therefore, present invention additionally comprises a kind of method for producing preparaton of the present invention, the preferred reality of the preparaton is preferably produced One of scheme is applied, such as especially embodiment A and AA method.
This method comprises the following steps, is preferably made up of the following steps：A) individually successively, in pairs, two or more Simultaneously or all simultaneously, sterol ester and solubilizer are preferably all in turn added, are added particularly preferable as the first material Before entering sterol ester and the then heating in step b), among or afterwards, exist before the heating particularly preferably in step b) Other materials are added in stainless steel；B) mixture of the material being individually initially added or two or more materials is heated Temperature to more than the fusing point of sterol ester；C) mixture heated is mixed to the time of 1-60 minutes under 500-2500rpm, To obtain a homogeneous mixture.
In principle, possible gel capsule includes all types of hard and soft capsules, and it is by natural origin, such as plant And/or animal origin, and the material of synthesis source, such as synthetically produced polymer or by biological technique method production Polymer production.It is preferred that the gel capsule being made up of plant material and be made up of synthetic polymer those.
Such material, its production and to obtain and also have it to be processed into gel capsule be many to those skilled in the art Well known.Basic summary for example can be in the Lehrbuch der Pharmazeutischen Technologie [medicines Technology textbook], such as section IV, " Die Herstellung von Hart-und Weichgelatinekapseln " are [hard With the production of Perle], author：58-82 pages of Kurt H.Bauer, Freiburg, the, or the 8th edition in the textbook, 14th chapter, the 6th sub- chapter, the 344-355 pages, and also many other standard textbooks find.For example, the feature of hard shell capsules exists In capsule as the production of two parts coherent capsulae vacuus, the fact that the latter only fills and closed after manufacturing.Big In most cases, hard shell capsules produced in so-called infusion process by the aqueous solution (S.Stegmann, PZ Prisma, 5,42-56, 1998).Prior art for the injection by starch or manufacturing of gelatin pharmaceutical hard capsule is summarized by L.Eith etc. in Drug Dev.Ind.Pharm., provided in 12,2113-2126 (1986).Production is hard and the entirely different method of Perle describes In W.Fahrig and U.Hofer, Die Kapsel [capsule], Wissenschaftliche Verlagsgesellschaft MbH Stuttgart, 1983, in the 58-82 pages.
Capsule and its production and application can equally be found in many patent specifications.Particularly for medicinal application, food The known manufacturer of the capsule of product enriching substance etc. is following company：Catalent (R.P.Scherer has been incorporated into Catalent), Banner, Capsugel, Accucaps, Swiss Caps (are incorporated to Aenova).Corresponding publication and patent application and specially Profit is as known to these and many other companies.
It is following to mention as an example：WO2014/202754 discloses the flexible glue for including acyl gellan gum, starch and plasticizer Capsule；US 20010098784 discloses the capsule comprising galenical；US6790495B discloses the life of amyloid soft capsule Production and the equipment for its production；WO2007/116062 discloses the capsule comprising plant extracts or melt extrusion thing； US2010291197 discloses the capsule for producing by melt extrusion and being made up of polymeric material；EP2042180A1 is disclosed Comprising the emulsifying agent of phytosterol, 10-100% triglycerides, 1-40%HLB values more than 12 and 1-80%HLB values less than 11 Coemulsifier, self-emulsifying filler and water-free soft capsule；WO2002074861 discloses polyalcohol as gel former Purposes and cold water soluble gelatin gel capsule also therefrom；US2004060258 is disclosed by rotating die head Method produces capsule, especially soft capsule；It is molten that DE2237545A1 discloses a kind of polymer by evaporation in organic solvent Liquid and the method for producing microcapsules；EP1138322A2 discloses hard shell capsules and EP1136070 (A1) discloses soft capsule, its use Way and production, their polymer, structures of each self-contained vinyl esters and optional other monomers for example for medicinal application Improve excipient and also have other conventional shell components；EP1926480 (B1) discloses soft capsule and its production, wherein soft capsule Shell is based on polyvinylesters-polyethyleneglycol-graft copolymer；US55699466A discloses the filling combination for elastic soft capsules Thing；US5505961A discloses gelatine capsule；US2003085487A discloses the equipment for producing soft capsule； US2003232076A discloses chewable soft capsule.
Therefore, present invention additionally comprises one kind production to include preparaton of the present invention, the preferred embodiments of preferred formulations it One, such as method of especially embodiment A and AA gel capsule.In principle, it is all known to a person skilled in the art Material and production method and step can be used as hydrogel capsule materials, condition be present in it is compatible with preparaton of the present invention Property.
The compatibility can be evaluated easily, be primarily based on the material for preparaton and capsule material, second by making With the simple experiment of appropriate capsule material.
As shown in the Examples, the use of independent emulsifying agent can not obtain good self-emulsifying result.However, when two kinds of mixing During emulsifying agent, extraordinary result and self-emulsifying systems are obtained.This is in SUN FM 580 (lecithin lipid) and Systerna SP It is especially surprising in the case of 70 (sugar esters), turn because the Systerna products are not dissolved in individually in the preparaton and must used Son-stator intermixture disperses.However, significantly improve self-emulsifying using a small amount of Systerna products.
Similarly find to add aliphatic acid acid ascorbyl ester such as palmitic acid Vitamin C in the preparaton comprising lecithin lipid Acid esters and/or aliphatic acid acid ascorbyl ester, especially ascorbyl palmitate significantly improve self-emulsifying in stomach model Can, but ascorbyl palmitate first these temperature in the oil it is insoluble, secondly under the conditions of these pH as it is cloudy from Sub- emulsifying agent is not charged and therefore only shows low-down emulsion-stabilizing activity and also has low molten in water-bearing media Xie Du.Finally, similarly find that polysorbate phase is separated with sterol ester, such as in the case of polysorbate 80, but Be lecithin lipid is added in the system prevent the separation and when these material height are used alone compared with clearly Ground improves automatic emulsifying performance.
In a word, it can be noted that aliphatic acid acid ascorbyl ester, preferably ascorbyl palmitate and also lecithin lipid and The combination of polysorbate, preferably polysorbate 80 obtains particularly preferred performance, especially as comprising oil as other components The extraordinary automatic emulsifying performance of sterol ester preparaton, therefore the combination is that very particularly preferably embodiment of the invention is (real Apply option A), wherein to observe that aforementioned proportion (wide scope and also has correspondingly disclosed narrower and preferred limit, as especially The combination of the corresponding preferred scope of also various components) and if necessary there may be other optional compositions.Especially excellent In the embodiment AA of choosing, in the absence of optional other compositions.
Embodiment
The production of preparaton
Phytosterin ester and emulsifying agent are merged and are heated to 60 DEG C to avoid crystallizing and/or preferably reduce viscosity.Then Mixed (Thinky mixers ARE-250 (Thinky Corporation, USA) 1min, Huo Zhe under 2000rpm In Ultra-Turrax pipes driver (IKA, Germany) under 2000rpm about 30min).Make in the presence of all raw materials are with liquid With Thinky mixers, and when at least one raw material exists as semi-solid or solid matter and can not be easily dissolved in liquid plant Thing sterol ester phase uses at about 60 DEG C during liquefied phytosterin ester phase (such as protein, ascorbyl palmitate) Ultra-Turrax mixers.The preparaton is set to reach room temperature (about 20-25 DEG C), it is any to allow to be formed in process of production Possible foam dissolving is overnight (i.e. after about 8-12 hours), and check phase separation.If having no phase separation, following applications are carried out Test.
All results shown below have the data in terms of weight %.
Using test
Artificial liquid soluble in the stomach：
2g 1M hydrochloric acid is added in 900ml distilled water, pH is adjusted to 1.6 with 1M hydrochloric acid and is supplemented to 1 using distilled water Rise.
Small intestine solution：
By 0.42g NaOH pieces, 3.95g NaH2PO4*H2O and 6.19g NaCl are dissolved in 900ml distilled water.Use hydroxide PH is adjusted to 6.5 and the solution is supplemented into 1 liter using distilled water by sodium solution.
Tested in stomach model：
The phytosterin ester/emulsifying agent preparaton is heated to about 60 DEG C to obtain homogeneous liquid phase.Then by the 100ml stomaches Solution and the 100ml small intestine solution are each heated to 37-38 DEG C, and add the 1g preparatons in each case.By the system Stir 1 hour at 200 rpm, then visual inspection.It the results are shown in Table 3.
Caco2 models
Equally these preparatons are tested in so-called Caco2 models.This includes the administration of detection preparaton to cholesterine The effect of absorption in Caco2 cells.Whether this can with how well reduce the courage of cell for the sterol ester in preparaton The measurement of cholesterol absorption.Higher (i.e. lower) is prevented to cholesterol absorption, preparaton is more effective.
Principle after Caco2 tests：
Caco2 cells are cultivated on perforated membrane；The polarization structure of cell, absorb nutrient (in this case in top surface：Cholesteric Alcohol) and secrete them in basal plane.
Detect and cholesteric transport by while supplement the influence degree of phytosterol and various excipient compositions.
Testing procedure：Cultivate cell；Produce so-called mixed micelle；Measure cytotoxicity simultaneously determines working concentration；Measurement Twice of cholesterol concentration (6 and 24 hours after supplement is started) in basal compartment, measurement in each case is repeated 3 times.
Cytotoxicity test：All test substances can use 150 μ g/ml concentration without damaging cells；Choose work Concentration 50-100-150 μ g/ml.
In order to form micella, it will keep constant for the cholesteric amount of all treatment groups.In the solution of applied on top During analysis, it is determined that it (is probably due to the cholesterine during micelle forma-tion that the cholesterol content in produced micella, which changes, Intentional displacement mutually with phytosterol causes).
Therefore, by the actual cholesterol content of cholesterol absorption or the calibration of the output results transported to make-up solution.Sterol used Ester：
Vegapure 95E, from BASF SE, comprising a small amount of various tocopherols and ascorbyl palmitate as anti- Oxidant；Sterol ester ratio：At least 97% (area percent)；Free sterol ratio：At most 6% (area percent).
Solubilizer used：
- TWEEN-20：Polyoxyethylene (20) sorbitan mono-laurate, E432
- polysorbate 80：Polyoxyethylene (20) dehydrating sorbitol monooleate, E433, " Tween80 "
-Lipoid P 75：Lecithin lipid fraction and phospholipid from soybean, comprising about 75% phosphatidyl choline, 7% Phosphatidyl-ethanolamine
-Prefera SSL 6000：Esterification degree is 100-140 stearoyl -2- sodium lactates
-Lametop P 65：The FDA specifications DATEM (diacetyl tartaric acids of DATEM=monoglycerides and diglyceride Ester), E472e
-Phosal 40IP：Include about 40% soy phosphatidylcholine and sunflower oil and the also liquid of mixed tocopherol class Body composition
-MCT：Medium chain triglyceride, mainly comprising C8-C10The oil of aliphatic acid
-Lecico SUN FM 580：Sunflower lecithin class from Lecico；Liquid, enzyme urge modified sunflower lecithin Lipid, 56%AU
-CholestOff：From NatureMade, USA commercially available contrast product；Include plant sterol and stanol.
The preparaton of table 1 below (1a and 1b) display test.
Table 1a：Composition
Table 1b：Composition (table 1a continues)
Result of the test：
Table 1 (1a and b)：Preparaton-composition of test
Fig. 1：The cholesterol content (% of the initial concentration of administration) of basic accepting medium after 6 hours
Fig. 2：The cholesterol content (% of the initial concentration of administration) of basic accepting medium after 24 hours
Fig. 3：Cholesterine (" CHOL ") is individually and the infrared spectrum of micellar solution that is combined with tested preparaton
Fig. 4：The PCA analyses of the micellar solution of the cholesterine (CHOL) combined individually and with various test substances (C1-C10)
Fig. 5：It is related to the result of table 4
Further result (data for being related to table 3) from Caco2 models
Table 2：Compared with the Vegapure 95E as independent material, phytosterol-excipient composition is to cholesteric fortune The influence sent
Table 3：Further result from Caco2 models
Table 4：The result (" sterol ester "=Vegapure 95E from BASF) tested in stomach model
Table 2：Compared with the Vegapure 95E as independent material, phytosterol-excipient composition is to cholesteric fortune The influence sent
Measurement cholesterine during micelle forma-tion is replaced by phytosterol
Cholesterine and phytosterol be poorly water soluble and in vivo with the bile salt one in aliphatic acid and mixed micelle Rise and transport.
Cholesterine is counted as phytosterol from the displacement in micella reduces the important mechanism of cholesteric effect.
The purpose of the measurement is influence of the test substances to be determined to cholesterol concentration in gained micellar solution, thus to obtain Instruction to cholesterine from the possibility displacement in micella.
Substances are used for external micelle forma-tion with 5 various concentrations together with the cholesterol concentration of determination.
Gained micelle emulsion is detected by using the infra-red sepectrometry of SpeCCs analyzers (Cetics Healthcare).
At first glance infrared spectrum (Fig. 3) due to the chemical constitution similitude of cholesterine and phytosterol and only it is slight not Together.Further evaluation is carried out using principal component analysis (PC) statistics, can determine the similarity of sample whereby.
Cholesterine (CHOL) is individually and the PCA of micellar solution that combine with various test substances (C1-C10) analyzes (Fig. 4)
As a result：Preparaton comprising Lipoid P75+ water most differs markedly from pure cholesterine micella, followed by Vegapure 95E, polysorbate 80, Lametop P65+MCT and Prefera SSL 6000, and this is considered as cholesterine from micella In displacement measurement.
Table 3：Influence of the combination of Caco2 models PRELIMINARY RESULTS-phytosterin ester and emulsifying agent to cholesteric transport
Result in table 3 shows that cholesteric transport may be than list when using the combination of phytosterin ester and emulsifying agent It is solely larger impacted using phytosterin ester.
Table 4 illustrates the evaluation of the test of the preparaton from table 3.
Fig. 5 illustrates the selection result in the Caco2 tests of the preparaton from table 3.
It is related to the evaluation of table 4：Visual assessment：Score value
1=is uniform, surface oil-free
2=is substantially uniform, and surface, which has, small arrives medium oil droplet
There is notable oil reservoir on the medium turbidity of 3=, surface
The muddy appearance that 4=slightly turns white, there is stiff oil reservoir on the surface
5=is substantially completely separated without emulsifying effectiveness
Table 4：The result (" sterol ester "=Vegapure 95E from BASF) of formula is surveyed in stomach model；Also Fig. 5 is seen
Table 4-continuous：The result (" sterol ester "=Vegapure 95E from BASF) tested in stomach model；Also figure is seen 5

Claims (15)

1. a kind of preparaton for gel capsule, include sterol ester and solubilizer substantially.
2. preparaton according to claim 1, wherein the sterol ester is by the sterol (phytosterol) of plant origin or its hydrogenation Analog-stanols obtains.
3. preparaton according to claim 2, wherein the sterol ester is obtained by sterol.
4. preparaton as claimed in one of claims 1-3, wherein the aliphatic acid for being esterified is the aliphatic acid of natural origin, The aliphatic acid of preferred plant or marine source.
5. preparaton as claimed in one of claims 1-4, wherein the aliphatic acid is single insatiable hunger and/or polyunsaturated fat Acid, preferably polyunsaturated fatty acid.
6. preparaton according to claim 5, wherein it is described it is fatty acid-based in the fatty acid part with least 30 weight %'s Amount includes omega-fatty acid such as EPA and/or DHA.
7. preparaton as claimed in one of claims 1-6, wherein as solubilizer being at least one to be selected from poly- sorbic acid The material of ester, lecithin lipid and stearoyl -2- sodium lactates.
8. preparaton according to claim 7, wherein at least one fatty acid ester selected from ascorbic acid, arabo-ascorbic acid be present Fatty acid ester or material with sucrose fatty acid ester, preferably sucrose is as the sugar in sugar ester.
9. preparaton according to claim 8, wherein selection aliphatic acid acid ascorbyl ester, preferably ascorbyl palmitate, with And also lecithin lipid and polysorbate, preferably polysorbate 80.
10. preparaton as claimed in one of claims 1-7, wherein the preparaton only volume in addition to sterol ester and solubilizer A small amount of water and/or oil are included outside.
11. a kind of gel capsule, include the preparaton according to any one of preceding claims.
12. gel capsule according to claim 11, in soft or form of hard gelatin capsules.
13. according to the gel capsule of claim 11 or 12, as food supplement or as medicine.
A kind of 14. method for producing preparaton as claimed in one of claims 1-10.
A kind of 15. method for producing the gel capsule according to claim 11 or 12.
CN201680022726.2A 2015-04-23 2016-04-20 Gel capsules containing sterols and solubilizing agents Active CN107530358B (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP15164868 2015-04-23
EP15164868.0 2015-04-23
EP15165398 2015-04-28
EP15165398.7 2015-04-28
PCT/EP2016/058683 WO2016169941A1 (en) 2015-04-23 2016-04-20 Gel capsule containing sterol and solubilising agent

Publications (2)

Publication Number Publication Date
CN107530358A true CN107530358A (en) 2018-01-02
CN107530358B CN107530358B (en) 2021-08-06

Family

ID=55794978

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201680022726.2A Active CN107530358B (en) 2015-04-23 2016-04-20 Gel capsules containing sterols and solubilizing agents

Country Status (7)

Country Link
US (1) US10188133B2 (en)
EP (1) EP3285749B1 (en)
JP (2) JP2018516871A (en)
CN (1) CN107530358B (en)
AU (1) AU2016251535B2 (en)
BR (1) BR112017022523B1 (en)
WO (1) WO2016169941A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11419350B2 (en) 2016-07-01 2022-08-23 Corbion Biotech, Inc. Feed ingredients comprising lysed microbial cells
US10835456B2 (en) 2016-07-19 2020-11-17 Basf Se Propyl gallate-containing vitamin preparations
WO2021202493A1 (en) 2020-03-31 2021-10-07 L'oreal Ceramide containing capsules, ceramide compositions, and cosmetic compositions thereof
FR3113244B1 (en) 2020-08-07 2023-03-17 Oreal Capsules containing ceramide, ceramide compositions, and related cosmetic compositions
US11007134B1 (en) 2020-03-31 2021-05-18 L'oreal Ceramide containing capsules, ceramide compositions, and cosmetic compositions thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050153948A1 (en) * 2003-11-20 2005-07-14 Zomanex, Llc Methods and formulations for the treatment of medical conditions related to elevated dihydrotestosterone
US20070254088A1 (en) * 2006-05-01 2007-11-01 Forbes Medi-Tech Inc. Composition comprising one or more esterified phytosterols and/or phytostanols into which are solubilized one or more unesterified phytosterols and/or phytostanols, in order to achieve therapeutic and formulation benefits
EP2042180A1 (en) * 2007-09-28 2009-04-01 Swiss Caps Rechte und Lizenzen AG Preparations containing phytosterol

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2237545A1 (en) 1972-07-31 1974-02-14 Basf Ag Microcapsule material - of polymer comprising hydrophobic and hydrophilic groups and applied to paper to give typing copies without carbon paper use
US5505961A (en) 1993-08-05 1996-04-09 R. P. Scherer Corporation Gelatin capsules containing a highly concentrated acetaminophen solution
US5569466A (en) 1995-05-17 1996-10-29 R. P. Scherer Corporation Fill compositions for soft elastic gel capsules
FI111513B (en) * 1998-05-06 2003-08-15 Raisio Benecol Oy Novel compositions of phytosterol and phytostanol fatty acid esters, products containing them and processes for their preparation
NZ501169A (en) * 1998-11-26 2001-05-25 F Fatty acid esters of phytosterol and phytostanol
DE59911807D1 (en) 1999-11-19 2005-04-28 Swiss Caps Rechte & Lizenzen A process for producing a starch-containing shaped body, homogenized starch-containing mass and apparatus for producing a soft capsule
DE10012063A1 (en) 2000-03-14 2001-09-20 Basf Ag Soft plasticizer-free capsules for use in pharmaceuticals, cosmetics, detergents or plant protectants are made from a polymers obtained by polymerizing a vinyl ester in presence of a polyether substrate
DE10015468A1 (en) 2000-03-29 2001-10-11 Basf Ag Hard capsules containing polymers and vinyl esters and polyethers, their use and production
ES2257998T3 (en) 2000-12-20 2006-08-16 Swiss Caps Rechte Und Lizenzen Ag PROCEDURE FOR ROTATING TROQUELING AND FILLING WEDGE TO MANUFACTURE CAPSULES, IN SPECIAL SOFT CAPSULES.
EP1241226A1 (en) 2001-03-16 2002-09-18 Swiss Caps Rechte und Lizenzen AG Use of a polyol as a gelling agent for cold-water soluble gelatin gels. Films, articles and capsules formed therefrom
US6884060B2 (en) 2001-11-02 2005-04-26 R.P. Scherer Technologies, Inc. Apparatus for manufacturing encapsulated products
JP4226846B2 (en) 2002-06-07 2009-02-18 キャタレント・ジャパン株式会社 Soft capsule that can disintegrate in the oral cavity
DE10253111A1 (en) * 2002-11-13 2004-05-27 Basf Ag Powdered formulation used e.g. as food additive or pharmaceutical for preventing arteriosclerosis and hyperlipemia, contains phytosterol
US20050032757A1 (en) * 2003-08-06 2005-02-10 Cho Suk H. Nutritional supplements
ATE557075T1 (en) * 2004-03-19 2012-05-15 Mitsubishi Chem Corp DEGRADATION INHIBITOR
JP2006273765A (en) * 2005-03-30 2006-10-12 Gotoo Corporation:Kk Constipation ameliorator, use thereof, fecal odor ameliorator, and use thereof
DE102005043172A1 (en) 2005-09-09 2007-03-15 Basf Ag Process for the preparation of soft capsule shells based on polyvinyl alcohol-polyethylene glycol graft copolymers
CH699154B1 (en) 2006-04-11 2010-01-29 Swiss Caps Rechte & Lizenzen Capsule containing plant preparations.
JP5037140B2 (en) * 2007-01-09 2012-09-26 理研ビタミン株式会社 L-ascorbic acid fatty acid ester-containing preparation
CH704033B1 (en) 2007-03-26 2012-05-15 Swiss Caps Rechte Und Lizenzen Ag Capsules containing herbal preparations.
EP2042165A1 (en) 2007-09-28 2009-04-01 Swiss Caps Rechte und Lizenzen AG Hot-melt filled soft capsules
JP2013147456A (en) * 2012-01-19 2013-08-01 Fuji Oil Co Ltd Antioxidant
EP2815745A1 (en) 2013-06-21 2014-12-24 Swiss Caps Rechte und Lizenzen AG Soft shell capsule and process for its manufacture
EP3091852A1 (en) 2013-12-18 2016-11-16 Basf Se Stabilized phycocyanin for blue color
BR112017022430A2 (en) 2015-04-22 2018-07-10 Basf Se Dispersions, processes for preparing dispersions and solid particles from dispersions, use of dispersions, preparations, and solid particles.

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050153948A1 (en) * 2003-11-20 2005-07-14 Zomanex, Llc Methods and formulations for the treatment of medical conditions related to elevated dihydrotestosterone
US20070254088A1 (en) * 2006-05-01 2007-11-01 Forbes Medi-Tech Inc. Composition comprising one or more esterified phytosterols and/or phytostanols into which are solubilized one or more unesterified phytosterols and/or phytostanols, in order to achieve therapeutic and formulation benefits
EP2042180A1 (en) * 2007-09-28 2009-04-01 Swiss Caps Rechte und Lizenzen AG Preparations containing phytosterol

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
金青哲 主编: "《功能性脂质》", 31 August 2013, 中国轻工业出版社 *

Also Published As

Publication number Publication date
US10188133B2 (en) 2019-01-29
EP3285749B1 (en) 2024-06-05
US20180110254A1 (en) 2018-04-26
AU2016251535A1 (en) 2017-12-07
BR112017022523A2 (en) 2018-07-10
JP2018516871A (en) 2018-06-28
JP7282068B2 (en) 2023-05-26
AU2016251535B2 (en) 2021-02-04
BR112017022523B1 (en) 2023-12-19
CN107530358B (en) 2021-08-06
WO2016169941A1 (en) 2016-10-27
EP3285749A1 (en) 2018-02-28
JP2021040650A (en) 2021-03-18

Similar Documents

Publication Publication Date Title
CN107530358A (en) Gel capsule containing sterol and solubilizer
Salvia-Trujillo et al. In vitro and in vivo study of fucoxanthin bioavailability from nanoemulsion-based delivery systems: Impact of lipid carrier type
DE69818704T2 (en) METHOD FOR IMPROVING THE ABSORPTION AND TRANSPORT OF LIPID-SOLUBLE COMPOUNDS BY MEANS OF STRUCTURED GLYCERIDES
Wu et al. Curcumin-loaded liposomes prepared from bovine milk and krill phospholipids: Effects of chemical composition on storage stability, in-vitro digestibility and anti-hyperglycemic properties
ES2317017T3 (en) COMPOSITIONS OF SUPPLY OF PHARMACO ESTER OF ALFA-HYDROXIACIDE AND METHODS OF USE.
Xu et al. Study on the relationship between lutein bioaccessibility and in vitro lipid digestion of nanostructured lipid carriers with different interface structures
JP2000026283A (en) Powder composition containing oily composition
JPWO2018131620A1 (en) Drug-containing fat emulsion and method for producing the same
EP2129387A2 (en) Capsule containing plant preparations
JP5269373B2 (en) Liquid composition for soft capsule filling
Bhat et al. Influence of fatty acids in edible oils on lutein micellization and permeation in a simulated digestion model
JP2000024487A (en) Emulsified composition containing oily composition
KR101503474B1 (en) Liquid composition for soft-capsule filling
WO2011027605A1 (en) Liquid composition to be filled in soft capsules
WO2020260577A1 (en) Oil-in-water emulsion of nano-sized self-emulsified particulates
JP2000026884A (en) Powder composition containing oily composition
Amran et al. Superolein based intravenous lipid emulsion 20% w/w physicochemical characterization, stability and its effect on liver status
US20230381208A1 (en) Oral cannabinoid formulation comprising medium chain triglycerides and tocopheryl phosphates
US20230381207A1 (en) Oral cannabinoid formulation comprising tocopheryl phosphates and long chain triglycerides or long chain fatty acids
JP2019085349A (en) Composition for ingestion containing insoluble substance, method for improving gastrointestinal absorption of insoluble substance, and method for improving intragastric emulsion stability of oil-in-water emulsion containing insoluble substance
JP5156458B2 (en) Liquid composition for soft capsule filling
CN115844015A (en) Lycopene oil, lycopene preparation and application thereof
JP2023522146A (en) Sunflower phospholipid composition containing phosphatidylcholine
JP2000024482A (en) Emulsified composition containing oily composition
US20160081935A1 (en) Dosage forms for oral administration of active substances

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant